Currently, intravaginal barrier and intrauterine contraceptive devices, with or without hormones, are available to inhibit ovulation and to prevent sperm migration into the cervix and fertilization (Roy, “Status of Research and Development of Vaginal Contraceptive Rings as Fertility Control Method in the Female,” Research Frontiers in Fertility Regulation, Family Health Network International Bulletin 2(4):1-10 (2000). A literature search for non-hormonal, non-toxic, and non-invasive contraceptive agents, as well as the anti-microbial and anti-viral (U.S. Pat. No. 5,595,980 to Brode) agents revealed that metal ions and their derivatives, such as calcium chloride, sodium chloride, magnesium chloride, copper, and ferrous sulfate act as spermicidal and/or spermiostatic agents (U.S. Pat. No. 4,959,216 to Daunter). Copper sulfate has been used in intrauterine devices (“IUDs”) as a spermicidal agent. It is known that sulfhydryl groups are essential components of certain vital enzymes necessary for stability of the sperm. The copper-based agents are toxic due to their sulfhydryl binding properties and thus cause a direct deleterious effect on sperm. Copper also influences midcycle human cervical mucus by causing lysis of the mucus material, changing the physico-chemical properties of the mucus resulting in a decrease in sperm penetration (Shoham et al., “Influence of Different Copper Wires on Human Sperm Penetration Into Bovine Cervical Mucus,” In Vitro. Contraception 36(3):327-34 (1987)).
Diveley (U.S. Pat. No. 3,950,366) tested metal salts of 1,1,5,5-tetrasubtituted-dithiobiurets as spermiostatic agents. Light metals such as sodium and potassium, alkaline earth metals such as calcium and barium, and heavy metals such as zinc, cadmium, tin, mercury, copper, nickel, chromium, iron, manganese, and cobalt, given orally as chelates, have been shown to form dithiobiuret salts, which act as contraceptive and pregnancy terminators. Sawan et al., (U.S. Pat. No. 5,224,493) showed that insoluble, inorganic metallic salts and oxides of silver, magnesium, zinc, copper, cadmium or arsenic can be used as anti-inflammatory agents. Brode used benzylalkonium chloride, octoxynol-9, nonoxyl-9, ricinoleic acid, and phenol mercury acetates as spermicides delivered via hydrophobically modified polysaccharides as a polymeric delivery system to reduce the potential for infection and sexually transmitted diseases (STD) (U.S. Pat. No. 5,595,980 to Brode).
Cellulose-based vehicles consisting of hydroxyethyl cellulose and hydroxyethyl methyl cellulose, or mixtures thereof, or optionally a cosmetic ingredient selected from the group consisting of water, ethyl alcohol, isopropyl alcohol, glycerin, glycerol, propylene glycol, and sorbitol, have also been used as delivery systems. Typical forms of delivery systems used vaginally include creams, lotions, gels, foams, sponges, suppositories, and films. Daunter used Cu-ethylenediaminetetraacetic acid/L-ascorbic acid, neuraminidase, and asialofetuin as fertility preventing agents which can be delivered via polyurethane or polyvinyl acetate discs (U.S. Pat. No. 4,959,216 to Daunter). The first two agents act on the cervical mucus to change it from the open cellular structure found at midcycle of the menstrual period to the closed structure that forms an impenetrable barrier for sperm. An ethylene vinyl acetate copolymer has also been used as a component of the matrix for the intravaginal device. Albumin increases the viscosity of the cervical mucus by diminishing the effect on ferning and spinnbarkeit. Albumin, dextran, and vinyl acetate were found to affect mucus spinnbarkeit due to the polymerization of the mucous glycoprotein, resulting in an increase in the viscosity of the cervical mucus. The spermicidal effect of certain devices was also based on their ability to change the vaginal pH to become more acidic (Olmsted et al., “The Rate at Which Human Sperm Are Immobilized and Killed by Mild Acidity,” Fertility And Sterility 73(4):687-693 (2000).
The success rate of a contraceptive depends not only upon the efficacy of the contraceptive method, but also upon the user's preference, reversibility, convenience, and compliance. Besides pregnancy, sexual relations can also transmit infection. It is thus beneficial that the design of new contraceptive devices should also consider the option of protecting women against transmission of sexually transmitted diseases (STDs) as well as against pregnancy. Hormone-based contraceptives have long been identified as posing an adverse metabolic risk, and are, in fact, contraindicated for individuals with a variety of cardiovascular conditions. Therefore, new contraceptive devices must be free of toxic compounds and hormones. In addition, a contraceptive method should allow women to use the method themselves in conjunction with normal management of their menstrual cycle as a tampon exchange month after month, thus enhancing the quality of life. However, a controlled release biodegradable delivery vehicle of bioactive agents for contraception over extended periods has not been developed thus far.
There is a pressing need to develop a non-hormonal, biocompatible, non-invasive, cost-effective, biodegradable, and convenient barrier device to prevent pregnancy and infection. The present invention is directed to overcoming these and other deficiencies in the art.